University of Kentucky Research Foundation

University of Pennsylvania

Thomas D Dziubla

Vladimir R Muzykantov

Eric Simone

David A Puleo

James Zach Hilt

John Mark Medley, Jr

Paritosh P Wattamwar

Theodora Asafo-Adjei

Eugene Kaplan

J Zach Hilt

Dipti Biswal

Carolyn T Jordan

David B Cochran

This invention concerns the incorporation of curcumin into the backbone of a hydrolytically degradable crosslinked hydrogel that utilizes poly(beta amino ester) (PBAE) chemistry to provide a tunable protective network with the ability to release at a controlled rate. Upon the introduction of these microparticle systems in to a free radical generating environment, the constituent amount of curcumin present in solution was improved in comparison to a free curcumin state. From these results, a kinetic rate model was developed to estimate oxidative consumption parameters of curcumin and curcumin monoacrylate and quantify theoretical levels of free radicals present depending on the rate of release of curcumin provided. Modeled curcumin conjugated PBAE microparticles improve translation and overall success in delivering a therapeutic agent that matches levels of oxidative stress.

Delivery systems and methods for reactive hydroxyl-containing compounds

The presently-disclosed subject matter includes compounds that comprise an initiator and an active agent that is covalently bonded to the initiator through a ring-opening polymerization process, an atom-transfer radical polymerization process, a Michael addition reaction, or a ring-opening metathesis polymerization process. In some embodiments the active agent includes simvastatin. The presently-disclosed subject matter also includes methods for making the compositions and methods for using the compositions to treat tissue wounds.

Polymeric prodrug

Antioxidant polymeric compounds are provided that comprise a plurality of monomeric portions, where each monomeric portion includes an antioxidant molecule interposed between at least two acrylate molecules, and where at least one acrylate molecule of each monomeric portion is linked by a diamine molecule to an acrylate molecule of an adjacent monomeric portion to thereby form the polymer. Methods of synthesizing polymeric compounds and methods of using the antioxidant polymeric compounds to reduce oxidative stress are also provided.

Compounds and methods for reducing oxidative stress

Compounds and methods for reducing the occurrence of a post-surgical adhesion are provided. The compounds can include acrylic acid groups and ethylene glycol groups, and can be directed to an area of damaged tissue by the incorporation of a fibrin targeting peptide. The compounds can further include a brush-like portion, capable of creating a steric barrier between a damaged tissue or organ and adjacent tissues or organs, and a targeting portion, capable of directing the compounds to a damaged tissue or organ. Methods of detecting damaged tissue and kits are also provided.

Compounds and methods for reducing the occurrence of post-surgical adhesions

A method of controlling a physical characteristic of polymeric nanocarrier-encapsulated protein particles includes altering or selecting a weight percentage of a hydrophobic polymer block in a total amphiphilic diblock copolymer of a primary emulsion of a double emulsion, freeze-thaw technique. The primary emulsion is formed using a freeze-thaw cycle of the amphiphilic diblock copolymer and a protein having a molecular weight of up to or equal to 300,000 Da. Selection of the hydrophobic polymer block percentage alters one or more characteristics of the resulting nanoparticles, such as shape. Thus, as one aspect, a method of producing filamentous polymeric nanocarrier-encapsulated protein (i.e., active enzyme) particles involves forming a primary emulsion using a freeze-thaw cycle of (i) an amphiphilic diblock copolymer, which has a molecular weight of about 10,000 to about 100,000 Da and comprises a conjugate of the hydrophobic polymer block and a hydrophilic polymer block, wherein the amphiphilic diblock copolymer comprises greater than 81% to about 95% by weight of the hydrophobic polymer block; and a protein having a molecular weight of up to or equal to about 300,000 Da. Various compositions comprising such filamentous-shaped nanocarrier particles, and methods of use for diagnosis and therapy are disclosed.

Method and compositions for polymer nanocarriers containing therapeutic molecules

The present invention is a method for encapsulating active protein in a polymeric nanocarrier. The instant method employs homogenization at subzero temperatures so that enzyme activity is retained. Enzymes which can be encapsulated by the present method include, for example, antioxidant enzymes and xenobiotic detoxifying enzymes. Encapsulation of an enzyme protects it from protease degradation and increases therapeutic half-life. Advantageously, polymeric nanoparticles of the invention are permeable to enzyme substrates and therefore enzymes encapsulated by the instant method can exert their effect without release from the nanocarrier. Methods for decomposing a reactive oxygen species, protecting against vascular oxidative stress, and detoxifying a xenobiotic are also provided.

Growing community of inventors

Frankfort, KY, United States of America

Thomas D Dziubla